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1.
Plant Cell Environ ; 47(2): 429-441, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37916615

RESUMO

The ratio of red light to far-red light (R:FR) is perceived by light receptors and consequently regulates plant architecture. Regulation of shoot branching by R:FR ratio involves plant hormones. However, the roles of strigolactone (SL), the key shoot branching hormone and the interplay of different hormones in the light regulation of shoot branching in tomato (Solanum lycopersicum) are elusive. Here, we found that defects in SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and CCD8 in tomato resulted in more lateral bud growth but failed to reverse the FR inhibition of lateral bud growth, which was associated with increased auxin synthesis and decreased synthesis of cytokinin (CK) and brassinosteroid (BR). Treatment of auxin also inhibited shoot branching in ccd mutants. However, CK released the FR inhibition of lateral bud growth in ccd mutants, concomitant with the upregulation of BR synthesis genes. Furthermore, plants that overexpressed BR synthesis gene showed more lateral bud growth and the shoot branching was less sensitive to the low R:FR ratio. The results indicate that SL synthesis is dispensable for light regulation of shoot branching in tomato. Auxin mediates the response to R:FR ratio to regulate shoot branching by suppressing CK and BR synthesis.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Luz Vermelha , Brotos de Planta/metabolismo , Citocininas , Lactonas , Ácidos Indolacéticos , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Langmuir ; 40(2): 1447-1460, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38175822

RESUMO

Enhancing the efficiency of photocatalysts in the removal of organic pollutants is of vital importance in wastewater treatment. In this work, a set of composite membranes that can be used for efficient removal of the organic dyes, such as methyl orange (MO), methylene blue (MB), and Congo red (CR), were prepared through coblending/electrospinning techniques using polyvinylidene fluoride (PVDF) as the substrate, polyvinylpyrrolidone (PVP) as the dispersing agent and wettability regulator, and cuprous oxide (Cu2O) as the photocatalyst. The results showed that Cu2O particles were well encapsulated in the electrospun PVDF/PVP fibers, and the composite membranes exhibited apparently enhanced hydrophilicity. Furthermore, compared with the pure Cu2O particles, the composite membranes not only showed a higher photocatalytic degradation ratio for MO (93.6%) but also showed a much higher degradation rate (62.4 mg/(mg·h)) in comparison with the other reported Cu2O-based composite photocatalytic materials in the literature. In addition, the membrane sample also had excellent recycling stability, and the retention rate of its removal ability maintained 92.1% after 5 times of recycling. Furthermore, the composite membranes also showed high removal ability toward MB and CR, with photocatalytic degradation ratios of 81.4 and 76.1%, respectively. This work indicates that the prepared PVDF/PVP-Cu2O composite membranes possess promising application prospects in wastewater treatment.

3.
Int Wound J ; 21(4): e14874, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606690

RESUMO

The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.


Assuntos
Diabetes Mellitus Tipo 2 , Pé Diabético , Humanos , Estudos Longitudinais , Pé Diabético/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , Pacientes Internados , Glucose , Triglicerídeos , Glicemia , Fatores de Risco , Biomarcadores
4.
J Exp Bot ; 74(18): 5722-5735, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37504507

RESUMO

Plant architecture imposes a large impact on crop yield. IDEAL PLANT ARCHITECTURE 1 (IPA1), which encodes a SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor, is a target of molecular design for improving grain yield. However, the roles of SPL transcription factors in regulating tomato (Solanum lycopersicum) plant architecture are unclear. Here, we show that the expression of SPL13 is down-regulated in the lateral buds of strigolactone (SL)-deficient ccd mutants and is induced by GR24 (a synthetic analog of SL). Knockout of SPL13 by CRISPR/Cas9 resulted in higher levels of cytokinins (CKs) and transcripts of the CK synthesis gene ISOPENTENYL TRANSFERASES 1 (IPT1) in the stem nodes, and more growth of lateral buds. GR24 suppresses CK synthesis and lateral bud growth in ccd mutants, but is not effective in spl13 mutants. On the other hand, silencing of the IPT1 gene inhibited bud growth of spl13 mutants. Interestingly, SL levels in root extracts and exudates are significantly increased in spl13 mutants. Molecular studies indicated that SPL13 directly represses the transcription of IPT1 and the SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and MORE AXILLARY GROWTH 1 (MAX1). The results demonstrate that SPL13 acts downstream of SL to suppress lateral bud growth by inhibiting CK synthesis in tomato. Tuning the expression of SPL13 is a potential approach for decreasing the number of lateral shoots in tomato.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Brotos de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Citocininas/metabolismo , Lactonas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Nanomedicine ; 47: 102618, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270453

RESUMO

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.


Assuntos
Traumatismo por Reperfusão , Animais , Ratos
6.
Heart Surg Forum ; 26(6): E770-E779, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38178357

RESUMO

PURPOSE: Global longitudinal strain (GLS) seems accurate for detecting subclinical myocardial dysfunction. This study aimed to determine the association between GLS and postoperative intensity of inotropic support in the patients undergoing heart valve surgery with preserved left ventricular ejection fraction. METHODS: 74 patients with preserved left ventricular ejection fraction who underwent valve surgery during the period between March 2021 and June 2022 were included in this prospective observational study. Transthoracic echocardiography including strain analysis with speckle tracking was performed before surgery. Patients were stratified according to the left ventricle (LV) GLS: LV-GLS ≥-16% (Impaired GLS group) and LV-GLS <-16% (Normal GLS group). The primary endpoint was postoperative vasoactive inotropic score. A high vasoactive inotropic score (VIS) was defined as a maximum VIS of ≥15 within 24 hours postoperatively. Postoperative adverse events, baseline clinical and echocardiographic data were also recorded. We invested the ability of preoperative GLS in predicting adverse postoperative outcomes, such as prolonged mechanical ventilation and the need for pharmacologic hemodynamic support after cardiac surgery. RESULTS: Seventy-four patients were included and analyzed in this study, including thirty-three in impaired GLS group and forty-one in normal GLS group. In-hospital mortality was 1.27% (1/74). Patients in impaired GLS group were more likely to have prolonged mechanical ventilation (p = 0.041). Multivariable logistic regression analysis revealed that the apical four-chamber view of the left ventricle (A4C)-GLS was significantly associated with high VIS (OR 1.373, p = 0.007). A4C-GLS had a sensitivity of 62.5% and a specificity of 89.66% for predicting high VIS (area under the curve, 0.78). The relationships between GLS and other secondary outcome measures were not statistically significant. The optimal cutoff of A4C-GLS for postoperative high vasoactive inotropic score was -10.85%. CONCLUSION: Preoperative LV dysfunction is an independent risk factor for postoperative high VIS. A4C-GLS may be a reliable tool in predicting high VIS after cardiac surgery. Those patients with impaired contractility were at high risk for elevated inotropic support and prolonged mechanical ventilation after cardiac surgery. These findings suggest an important role for echocardiographic GLS in perioperative assessment of cardiac function in the patients undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Disfunção Ventricular Esquerda , Humanos , Função Ventricular Esquerda , Volume Sistólico , Ventrículos do Coração/diagnóstico por imagem , Deformação Longitudinal Global , Prognóstico , Valvas Cardíacas
7.
Angew Chem Int Ed Engl ; 62(6): e202215372, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36480198

RESUMO

Developing conjugated small molecules (CSM) with intense NIR-II (1000-1700 nm) absorption for phototheranostic is highly desirable but remains a tremendous challenge due to a lack of reliable design guidelines. This study reports a high-performance NIR-II CSM for phototheranostic by tailoring molecular planarity. A series of CSM show bathochromic absorption extended to the NIR-II region upon the increasing thiophene number, but an excessive number of thiophene results in decreased NIR-IIa (1300-1400 nm) brightness and photothermal effects. Further introduction of terminal nonconjugated alkyl chain can enhance NIR-II absorption coefficient, NIR-IIa brightness, and photothermal effects. Mechanism studies ascribe this overall enhancement to molecular planarity stemming from the collective contribution of donor/side-chain engineering. This finding directs the design of NIR-II CSM by rational manipulating molecular planarity to perform 1064 nm mediated phototheranostic at high efficiency.

8.
Immunol Invest ; 46(7): 730-741, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28872972

RESUMO

The aim of this study was to investigate the expression and significance of T helper type 17 (Th17) and regulatory T (Treg) cells in severe pulmonary infection with gram-negative bacteria (GNB). The peripheral venous blood (PVB) and bronchoalveolar lavage fluid (BALF) were collected from patients receiving mechanical ventilation in the intensive care unit (ICU) owing to: (1) pulmonary GNB infection (group I) and (2) nonpulmonary infection (group NI). Patients from the two groups were matched based on their Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and were recruited in the same period. The levels of Th17 and Treg cells in the PVB and BALF were measured by flow cytometry. (1) The levels of Th17 and Treg cells in the PVB and BALF of the infection group (I) were significantly higher than those of the noninfection group (NI) (p < 0.01), and the levels decreased significantly after treatment (p < 0.01). (2) The Treg/Th17 cell ratio in the PVB and BALF of group I was significantly lower than those of group NI and after treatment (p < 0.01). (3) The levels of Th17 and Treg cells in the PVB and BALF could not predict the 28-day mortality (p > 0.05). The expression of Th17 and Treg cells was abnormal in patients with severe pulmonary GNB infection. Our data suggest an overactive immune response in the early stages of inflammation, but the levels of Treg and Th17 cells failed to predict the 28-day mortality.


Assuntos
Infecções por Bactérias Gram-Negativas/imunologia , Pulmão/imunologia , Infecções Respiratórias/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Idoso , Circulação Sanguínea/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Separação Celular , Feminino , Citometria de Fluxo , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Respiração Artificial , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/mortalidade , Análise de Sobrevida
9.
Adv Sci (Weinh) ; 11(30): e2309446, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38885368

RESUMO

Multidrug resistance to clinical chemotherapeutic drugs severely limits antitumor efficacy and patient survival. The integration of chemotherapy with photothermal therapy (PTT) and reactive nitrogen species has become a major strategy to enhance cancer treatment efficacy. Herein, a multifunctional peroxynitrite (ONOO-) nanogenerator (PBT/NO/Pt) for NIR-II fluorescence (NIR-II FL)/NIR-II photoacoustic (NIR-II PA) imaging-guided chemo/NIR-II PTT/ONOO- combination therapy is reported. The multifunction nanogenerator is developed by co-loading a pH-sensitive nitric oxide donor (DETA NONOate) and nicotinamide adenine dinucleotide phosphate oxidases trigger superoxide (O2 •-) generator chemotherapy drug (CDDP) to an NIR-II excitation-conjugated polyelectrolyte (PNC11BA). PNC11BA has non-conjugated alkyl chain segments in the polymer backbone and abundant positively charged phenylboronic acid in its side chains, which support the anti-quenching of NIR-II FL and the integration of DETA NONOate and CDDP into PBT/NO/Pt. In the acidic tumor microenvironment, the coordination bonds between CDDP and PNC11BA are cleaved, releasing CDDP for chemotherapeutic activity. The simultaneous release of nitric oxide (NO) and O2 •- rapidly leads to the in situ generation of the more cytotoxic reactive physiological nitrogen species ONOO-. In vitro and in vivo results prove that PBT/NO/Pt exhibited a markedly ONOO- enhanced chemo-photothermal synergistic therapy for SKOV3/DDP tumor by downregulating the intracellular glutathione and increasing CDDP-DNA adducts.


Assuntos
Ácidos Borônicos , Ácido Peroxinitroso , Terapia Fototérmica , Ácido Peroxinitroso/química , Terapia Fototérmica/métodos , Animais , Camundongos , Ácidos Borônicos/química , Polieletrólitos/química , Modelos Animais de Doenças , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral
10.
Chem Commun (Camb) ; 60(3): 332-335, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38073511

RESUMO

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

11.
Cancer Lett ; 604: 217268, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39321912

RESUMO

PARP inhibitors (PARPi) benefit only a small subset of patients with DNA homologous recombination (HR) defects. In addition, long-term administration of a PARPi can lead to the development of drug resistance. 2-Hydroxyglutarate (2HG) has long been known as an oncometabolite but is capable of inducing an HR defect, which makes tumor cells exquisitely sensitive to PARPi. To facilitate the translation of this discovery to the treatment of both HR-deficient and HR-proficient tumors, a liposomal formulation was developed for codelivery of 2HG and veliparib, a PARPi. A sequential loading protocol was developed such that the initial loading of 2HG into liposomes greatly facilitated the subsequent, pH gradient-driven remote loading of veliparib. The liposomes co-loaded with veliparib and 2HG exhibited favorable stability, slow kinetics of drug release, and targeted delivery to the tumor. Furthermore, the veliparib/2HG liposomes demonstrated enhanced anti-tumor activity in both PARPi-resistant BRCA mutant cancer and BRCA wildtype cancer by synergistically enhancing the defect in DNA repair. Moreover, combination of veliparib and 2HG via liposomal co-delivery also augmented the function of cytotoxic T cells by activating the STING pathway and downregulating PD-L1 expression via 2HG-induced hypermethylation.


Assuntos
Benzimidazóis , Reparo do DNA , Lipossomos , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Animais , Benzimidazóis/farmacologia , Benzimidazóis/administração & dosagem , Linhagem Celular Tumoral , Reparo do DNA/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Camundongos , Sinergismo Farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Proteína BRCA1/genética
12.
Front Endocrinol (Lausanne) ; 15: 1447750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39439559

RESUMO

Objective: This retrospective observational study investigates the heterogeneity of hepatic and pancreatic fat deposition and its implications for metabolic health in individuals with obesity. Methods: A total of 706 patients with obesity underwent an MRI to quantify liver and pancreatic fat. Patients were classified into four groups based on fat deposition: no fat (None), fatty pancreas only (NAFPD), fatty liver only (NAFLD), and both conditions (NAFLD+NAFPD). Biochemical profiles, insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR), and ß-cell function were analyzed. A series of multiple linear regressions were used to investigate the independent effects of characteristics on glucose, insulin, and C-peptide at 0h. Another multiple linear regression was performed to evaluate the effects of basic characteristics on average liver fat, mean pancreatic fat, and visceral fat. Results: The majority (76.63%) exhibited both NAFLD and NAFPD, highlighting the heterogeneity of fat deposition among individuals with obesity. Groups with fatty liver displayed significantly higher fasting glucose, insulin, C-peptide, and HOMA-IR levels than those without fatty liver (P < 0.01). Fatty pancreas alone did not significantly influence these metabolic parameters (P > 0.05). This underscores the greater metabolic impact of hepatic fat compared to pancreatic fat. Conclusions: The study confirms the complex heterogeneity of fat deposition in obesity, with the fatty liver being a more influential factor in metabolic disturbances than the fatty pancreas. The prevalent co-occurrence of NAFLD and NAFPD in this population underscores the need for targeted management strategies focusing on hepatic fat reduction to mitigate metabolic risk.


Assuntos
Resistência à Insulina , Fígado , Obesidade , Pâncreas , Humanos , Masculino , Feminino , Obesidade/metabolismo , Obesidade/complicações , Obesidade/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Pancreatopatias/metabolismo , Pancreatopatias/patologia , Imageamento por Ressonância Magnética , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/diagnóstico por imagem , Glicemia/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-37561624

RESUMO

The susceptibility of deep neural networks (DNNs) to adversarial intrusions, exemplified by adversarial examples, is well-documented. Conventional attacks implement unstructured, pixel-wise perturbations to mislead classifiers, which often results in a noticeable departure from natural samples and lacks human-perceptible interpretability. In this work, we present an adversarial attack strategy that implements fine-granularity, semantic-meaning-oriented structural perturbations. Our proposed methodology manipulates the semantic attributes of images through the use of disentangled latent codes. We engineer adversarial perturbations by manipulating either a single latent code or a combination thereof. To this end, we propose two unsupervised semantic manipulation strategies: one based on vector-disentangled representation and the other on feature map-disentangled representation, taking into consideration the complexity of the latent codes and the smoothness of the reconstructed images. Our empirical evaluations, conducted extensively on real-world image data, showcase the potency of our attacks, particularly against black-box classifiers. Furthermore, we establish the existence of a universal semantic adversarial example that is agnostic to specific images.

14.
ACS Appl Mater Interfaces ; 15(40): 47111-47124, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37768923

RESUMO

Recently, growing interest in self-powered devices has led to the invention of new energy conversion devices. Photo-thermoelectric generators (PTEGs) have rapidly developed for their ability to harvest both light and thermal energy, but these devices are overly dependent on the continuity of energy input and cannot sustain output in an emergency situation. In the current study, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/graphene oxide (GO)/graphene nanosheets (GNPs)/polyethylene glycol (PEG) phase-change composites (PCCs) were prepared with freeze-drying and vacuum-filling processes to acquire materials suitable for imparting energy storage characteristics to PTEGs. The melting and crystallization enthalpies of the PCCs fabricated based on the PEDOT:PSS/GO/GNP aerogels can reach 211.5 and 207.6 J g-1, respectively, which increase by nearly 5% compared with pure PEG, and the growth rate of thermal conductivity of the composites is as high as 262.7% (1.12 W m-1 K-1). Meanwhile, the excellent photothermal properties and high-temperature shape stability that pure PEG does not possess can also be imparted to PCCs by the aerogels. The PTEG assembled with PCCs and thermoelectric components can achieve a continuous output of over 1500 s after 300 s of light irradiation. After integrating the output of the device during the lamp on/off period, it is found that the total output of the device during the light-off period (8.4 V and 9.6 mW) can far exceed its total output during the light-on period (2.7 V and 4.4 mW). This work provides guidance for modulating the performance of PCCs and giving PTEGs the ability to operate under emergency or extremely harsh conditions and the prepared PTEGs are highly promising for practical use.

15.
Biomater Sci ; 11(13): 4644-4651, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37211916

RESUMO

Fluorescence imaging (FLI) in the near-infrared-II (NIR-II; 1000-1700 nm) window holds great potential for cancer metastasis imaging owing to its deep tissue penetration and a high signal-to-background ratio. However, currently reported organic NIR-II contrast agents generally present problems such as poor water solubility, low NIR-II fluorescence quantum yield (QY), short blood circulation half-life (t1/2), high injection doses, and undesirable tumor accumulation. In this study, an NIR-II small-molecule-based polymer (TQF-PSar) modified with four dense/hydrophilic polysarcosine (PSar) arms was prepared for efficient breast cancer pulmonary metastasis imaging. The NIR-II intensity of TQF-PSar (whose QY was calculated to be 1%) was 26.4-fold higher than that of the PEGylated nanoparticles (TQF-PEG NPs) at the same low dye dose (core TQF concentration: 2.5 µg mL-1). Moreover, owing to the ideal stealth character, TQF-PSar displayed a more prolonged blood circulation t1/2 (36.9 h) and better tumor accumulation capability than TQF-PEG NPs even at this low dye concentration. Finally, the successful use of TQF-PSar in noninvasive NIR-II FLI for breast cancer pulmonary metastasis was demonstrated in living mice.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Animais , Camundongos , Peptídeos , Sarcosina , Imagem Óptica/métodos , Neoplasias Pulmonares/diagnóstico por imagem
16.
Metabolism ; 143: 155559, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37044373

RESUMO

BACKGROUND AND AIMS: The liver plays a central role in controlling glucose and lipid metabolism. IDH2, a mitochondrial protein, controls TCA cycle flux. However, its role in regulating metabolism in obesity is still unclear. This study intends to investigate the impact of hepatic IDH2 expression on overnutrition-regulated glucose and lipid metabolism. METHODS: Hepatic IDH2 was knocked-out in mice by the approach of CRISPR-Cas9. Mice were subjected to starvation and refeeding for hepatic glucose and lipid studies in vivo. Primary hepatocytes and mouse normal liver cell line, AML12 cells were used for experiments in vitro. RESULTS: This study found that IDH2 protein levels were elevated in the livers of obese people and mice with high-fat diet consumption or hepatic steatosis. Liver IDH2-deletion mice (IDH2LKO) were resistant to high-fat diet-induced body weight gain, with lower serum glucose and TG levels, increased insulin sensitivity, and higher FGF21 secretion, despite the higher TG content in the liver. Consistently, overexpression of IDH2 in hepatocytes promoted gluconeogenesis and enhanced glycogenesis. By performing mass spectrometry and proteomics analyses, we further demonstrated that IDH2-deficiency in hepatocytes accelerated ATP production by increasing forward TCA cycle flux, thus promoting glycolysis pathway and decreasing glycogen synthesis at refeeding state, and inhibiting hepatic gluconeogenesis, increasing ß-oxidation during starvation. Moreover, experiments in vivo demonstrated that IDH2-knockout might not exacerbate hepatic inflammatory responses in the NASH model. CONCLUSIONS: Elevated hepatic IDH2 under over-nutrition state contributes to elevated gluconeogenesis and glycogen synthesis. Inhibition of IDH2 in the liver could be a potential therapeutic target for obesity and diabetes.


Assuntos
Gluconeogênese , Fígado , Animais , Camundongos , Dieta Hiperlipídica , Gluconeogênese/genética , Glucose/metabolismo , Glicogênio/metabolismo , Glicólise , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo
17.
Adv Healthc Mater ; 11(21): e2201158, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35943849

RESUMO

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT.


Assuntos
Nanopartículas , Terapia Fototérmica , Fototerapia , Linhagem Celular Tumoral , Imagem Óptica , Polímeros/química , Nanopartículas/química
18.
Medicine (Baltimore) ; 101(50): e32337, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36550865

RESUMO

Hypoxemia is 1 of the most common complications in the patients with acute Type A aortic dissection (ATAAD). This study aimed to summarize the risk factors, management strategies and long-term prognosis for postoperative hypoxemia in ATAAD patients. Baseline characteristics and clinical data of all the patients were collected. Patients were divided into 2 groups according to the PaO2/FiO2 after surgery: Hypoxemia group (n = 142) and Non-hypoxemia group (n = 68). The differences in gender, age, body mass index, operation time, cardiopulmonary bypass (CPB) time, aortic cross-clamping time, deep hypothermic circulatory arrest time, preoperative PaO2/FiO2, postoperative PaO2/FiO2, PaO2/FiO2 before extubating, time of mechanical ventilation, length of intensive care unit stay, length of hospital stay, in-hospital mortality, and overall mortality were compared between the 2 groups. The incidence of postoperative hypoxemia in this study was 67.6% (142/210). body mass index (26.4 ±â€…3.8 vs 24.4 ±â€…3.3kg/m2, P < .001) in the hypoxemia group were markedly higher and CPB time (196.3 ±â€…41.0 vs 181.0 ±â€…37.3 minutes, P = .010) in the hypoxemia group were significantly longer than those in the non-hypoxemia group. While preoperative PaO2/FiO2 (229.7 ±â€…91.4 vs 299.7 ±â€…101.2mmHg, P < .001) was significantly lower than those in the non-hypoxemia group. In the hypoxemia group, PaO2/FiO2 before extubating was significantly higher than that after operation, and the difference was significant. Logistic regression analysis showed that overweight (odds ratio [OR]: 1.113, P = .030), CPB time (OR: 1.009, P = .043) and preoperative PaO2/FiO2 (OR: 0.994, P = .001) were independent risk factors for postoperative hypoxemia. Further follow-up results showed no significant difference in long-term mortality between the 2 groups. Logistic regression analysis revealed that PaO2/FiO2 before extubating (OR: 0.985, P < .001), paraplegia (OR: 10.994, P = .019), acute renal failure (OR: 12.590, P < .001), re-operation (OR: 4.721, P = .014) and re-admission to intensive care unit (OR: 13.727, P = .001) were independent risk factors for long-term mortality. Our results showed that overweight and prolonged CPB time were risk factors for postoperative hypoxemia in ATAAD patients. While PaO2/FiO2 before extubating were independent risk factors for long-term mortality, indicating that active correction of hypoxemia and maintain a higher PaO2/FiO2 before extubating may help to improve the prognosis of the ATAAD patients.


Assuntos
Dissecção Aórtica , Síndrome do Desconforto Respiratório , Humanos , Sobrepeso/complicações , Hipóxia/epidemiologia , Hipóxia/etiologia , Dissecção Aórtica/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome do Desconforto Respiratório/complicações
19.
Adv Healthc Mater ; 11(15): e2200467, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35585025

RESUMO

The luminescence of traditional phosphorescence-based hypoxia probes is limited to the visible and first near-infrared wavelength regions (<1000 nm), which has defects of higher light scattering and lower penetration depth in contrast with the second near-infrared wavelength window (NIR-II, 1000-1700 nm) for optical bioimaging. Herein, 5,15-bis(2,6-bis(dodecyloxy)phenyl)-porphyrin platinum(II) (PpyPt) with J-aggregation induced NIR-II phosphorescence is reported. J-aggregates of PpyPt are confirmed by the X-ray diffraction data in the crystalline state. Moreover, the emission and excitation spectra of PpyPt in the solid states reveal NIR-II luminescence feature of PpyPt in J-aggregates. More importantly, by preparation of water-soluble PpyPt nanoparticles (PpyPt NPs4.76 ) with J-aggregates, it has NIR-II phosphorescent lifetime of microseconds and good oxygen-sensitivity in water. Moreover, the good biological hypoxia-sensing potential of PpyPt NPs4.76 is demonstrated in cells and 4T1-tumor-bearing mice. This study provides an efficient strategy to design NIR-II phosphorescent probe for sensitive tumor-hypoxia detection through the construction of J-aggregates.


Assuntos
Neoplasias , Porfirinas , Animais , Hipóxia/diagnóstico por imagem , Medições Luminescentes , Camundongos , Neoplasias/diagnóstico por imagem , Imagem Óptica , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Água
20.
Front Cardiovasc Med ; 9: 828015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355967

RESUMO

Background: The association between hypernatremia and delirium after cardiac surgery has rarely been investigated. This study aimed to determine whether hypernatremia increases the risk of delirium after exposure. Materials and Methods: From April 2016 to June 2021, 7,831 consecutive patients receiving cardiac surgery were screened for potential enrollment. The primary outcome was postoperative delirium (POD). For the respective case of delirium, 10 controls were matched according to the index date within the nested case-control design. Hypernatremia exposure was defined as serum sodium > 145 mmol/L within 7 days before the index date. A generalized estimation equation was performed to assess excess risks for POD associated with hypernatremia, adjusted for demographics and clinical variables. Results: About 7,277 patients were included in the final analyses. About 669 (9.2%) patients with POD were assigned to the case group, and 6,690 controls were identified from the whole population. About 66.5% of the cases and 36.3% of the controls had hypernatremia exposure. After being adjusted to certain well-recognized confounding factors, hypernatremia showed a significant correlation with increased risk of delirium after cardiac surgery (adjusted OR, 1.73; 95% CI, 1.41~2.12). An e-value analysis suggested the robustness to unmeasured confounding. Conclusions: Hypernatremia was associated with an increased risk of delirium after cardiac surgery. This finding could have implications for risk stratification, early detection, and management of delirium in patients receiving cardiac surgery.

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